Project Summary Gout impacts around 4% of the U.S. adult population and is the most common form of inflammatory arthritis in men. The incidence of gout is increasing worldwide. Gout significantly burdens the healthcare system, and is associated with both decreased work productivity and quality of life. With the ever-increasing impact of gout and its associated comorbidities on the population, investigation of novel translational mechanisms mediating gout flares as well as approaches to improving gout and hyperuricemia outcomes comprise an unmet and urgent medical need. When funded, the INvestigationS In Gout, Hyperuricemia, and comorbidiTies (INSIGHT) Center of Research Translation (CORT) included 4 active research projects and an Administrative Core focused on the theme, ?Gout, Hyperuricemia, and Associated Comorbidities?. Projects include studies to: determine if adenosine monophosphate-activated protein kinase (AMPK) activity metabolomics have promise as gout biomarkers independent of serum urate (P1), examine the influence of key gene-environment interactions within an internet study of gout flares (P2), unravel the functional genomics of urate transporter genes identified in previously reported genome wide association studies (P3), and investigate the mechanism of urate lowering therapy on renal function within VA STOP-GOUT (P4). Projects range from basic research translation of underlying genetics and inflammatory pathobiology of gout, to understanding mechanisms of CKD progression in gout, and translation of genetic interaction with environmental factors and medications, to precision medicine. The proposed revision project (P5) aims to utilize a novel emergency department based intervention to test methods to improve the care gout patients in the Deep South, with a secondary goal of concurrently enhancing participation of minorities in research. The revised INSIGHT CORT aims to: (1) Conduct five outstanding, innovative, and synergistic research projects drawing on the unique strengths of multidisciplinary research teams at our four major centers: University of Alabama at Birmingham, Harvard University, University of California San Diego, and now Vanderbilt University Medical Center; (2) Foster the development of pilot and feasibility projects and the development and application of new translational methods to research in gout and hyperuricemia and their associated major comorbidities, particularly CKD and metabolic syndrome; and (3) Promote training of translational investigators in current methods of research applicable to gout and hyperuricemia through enrichment activities overseen by our Administrative Core. The proposed revision project directly ties to the CORT through patient enrollment into the Gout CORT Registry and Biorepository, which contributes clinical data and biological samples to projects. The INSIGHT CORT is a multi-disciplinary translational research program at UAB and partner institutions. We have assembled an outstanding team and are uniquely prepared and strongly committed to scientific rigor, innovation, and development of knowledge and translational techniques.